ArticleThe international journal of neuropsychopharmacology2014
Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats.
Article in The international journal of neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Role of 5-HTBiomolecules · 2025Pooled it
- Effect of Vortioxetine on Cognitive Impairment in Patients With Major Depressive Disorder: A Systematic Review and Meta-analysis of Randomized Controlled Trials.The international journal of neuropsychopharmacology · 2022Pooled it
- A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Trial
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- Management strategies for burning mouth syndrome: a comprehensive review.Journal of oral & facial pain and headache · 2026Review
- Revisiting the Role of Serotonin in Attention-Deficit Hyperactivity Disorder: New Insights from Preclinical and Clinical Studies.Clinical drug investigation · 2025Review
- Effects of chronic stress on cognitive function - From neurobiology to intervention.Neurobiology of stress · 2024Review
- Poor Decision Making and Sociability Impairment Following Central Serotonin Reduction in Inducible TPH2-Knockdown Rats.International journal of molecular sciences · 2024Article
- Prefrontal serotonin depletion delays reversal learning and increases theta synchronization of the infralimbic-prelimbic-orbitofrontal prefrontal cortex circuit.Frontiers in pharmacology · 2024Article
- Vortioxetine Reverses Impairment of Visuospatial Memory and Cognitive Flexibility Induced by Degarelix as a Model of Androgen Deprivation Therapy in Rats.Neuroendocrinology · 2024Article
- Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment.Translational psychiatry · 2023Article
- Acute psilocybin enhances cognitive flexibility in rats.bioRxiv : the preprint server for biology · 2023Article
- Chronic stress induces NPD-like behavior in APPPS1 and WT mice with subtle differences in gene expression.Genes, brain, and behavior · 2021Article
- Impact of specific serotonin receptor modulation on behavioral flexibility.Pharmacology, biochemistry, and behavior · 2021Review
- Vortioxetine ameliorates anhedonic-like behaviour and promotes strategic cognitive performance in a rodent touchscreen task.Scientific reports · 2021Article
- Sequential reversal learning: a new touchscreen schedule for assessing cognitive flexibility in mice.Psychopharmacology · 2021Article
- Effect of a 5-HT7 Receptor Antagonist on Reversal Learning in the Rat Attentional Set-Shifting Test.ACS chemical neuroscience · 2021Article
- Serotonergic Innervations of the Orbitofrontal and Medial-prefrontal Cortices are Differentially Involved in Visual Discrimination and Reversal Learning in Rats.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants.Advances in neurobiology · 2021Article
- Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update.Therapeutic advances in psychopharmacology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Current treatments for depression, including serotonin-specific reuptake inhibitors (SSRIs), are only partially effective, with a high incidence of residual symptoms, relapse, and treatment resistance. Loss of cognitive flexibility, a component of depression, is associated with dysregulation of the prefrontal cortex. Reversal learning, a form of cognitive flexibility, is impaired by chronic stress, a risk factor for depression, and the stress-induced impairment in reversal learning is sensitive to chronic SSRI treatment, and is mimicked by serotonin (5-HT) depletion. Vortioxetine, a novel, multimodal-acting antidepressant, is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and inhibits the 5-HT transporter. Using adult male rats, we first investigated the direct effects of vortioxetine, acting at post-synaptic 5-HT receptors, on reversal learning that was compromised by 5-HT depletion using 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), effectively eliminating any contribution of 5-HT reuptake blockade. PCPA induced a reversal learning impairment that was alleviated by acute or sub-chronic vortioxetine administration, suggesting that post-synaptic 5-HT receptor activation contributes to the effects of vortioxetine. We then investigated the effects of chronic dietary administration of vortioxetine on reversal learning that had been compromised in intact animals exposed to chronic intermittent cold (CIC) stress, to assess vortioxetine's total pharmacological effect. CIC stress impaired reversal learning, and chronic vortioxetine administration prevented the reversal-learning deficit. Together, these results suggest that the direct effect of vortioxetine at 5-HT receptors may contribute to positive effects on cognitive flexibility deficits, and may enhance the effect of 5-HT reuptake blockade.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.